trandolapril and Coronary-Artery-Disease

Trandolapril is a well known angiotensin converting enzyme (ACE) inhibitor with many cardiovascular (CV) indications. The objectives of this article are to review the pharmacokinetics and pharmacodynamics properties of trandolapril and to focus on its clinical relevance in cardiovascular medicine. Various populations have been studied in large clinical trials including patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), diabetics, patients with hypertension (HTN), stable coronary artery disease (CAD) and prevention of proteinuria. Long-term treatment with trandolapril in patients with reduced left ventricular function soon after AMI significantly reduced the risk of overall mortality, mortality from CV causes, sudden death, and the development of severe CHF. Treatment with trandolapril after AMI complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe CHF as well. Moreover, trandolapril reduces progression to proteinuria in high-risk patients. Some of the advantages of trandolapril over other ACE inhibitors are the wide spectrum of patient populations studied, the well established dosage and its proven trough-to-peak effect ratios permitting a safe once-a-day administration.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Complications; Drug Administration Schedule; Heart Failure; Humans; Hypertension; Indoles; Myocardial Infarction; Proteinuria; Treatment Outcome; Ventricular Dysfunction, Left

Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction.. We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years.. Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced.. Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Coronary Disease; Female; Hospitalization; Humans; Indoles; Male; Middle Aged; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome

Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF) enrolled in the PEACE trial. We measured plasma OPN levels at baseline in 3567 CAD patients (mean age 64.5 ± 8.1 years, 81% men) by a sandwich chemiluminescent assay (coefficient of variation = 4.1%). OPN levels were natural log (Ln) transformed prior to analyses. We assessed whether Ln OPN levels were associated with the composite primary endpoint of cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure using multiple event multivariable Cox proportional hazards regression. Adjustment was performed for: (a) age and sex; (b) additional potential confounders; and (c) a parsimonious set of statistically significant 10 variates. During a median follow-up of 4.8 years, 416 adverse cardiovascular outcomes occurred in 366 patients. Ln OPN was significantly associated with the primary endpoint; HR (95% CI) = 1.56 (1.27, 1.92); P <0.001, and remained significant after adjustment for age and sex [1.31 (1.06, 1.61); P = 0.01] and after adjustment for relevant covariates [1.24 (1.01, 1.52); P = 0.04]. In a secondary analysis of the individual event types, Ln OPN was significantly associated with incident hospitalization for heart failure: HR (95% CI) = 2.04 (1.44, 2.89); P <0.001, even after adjustment for age, sex and additional relevant covariates. In conclusion, in patients with stable CAD and preserved EF on optimal medical therapy, plasma OPN levels were independently associated with the composite incident endpoint of adverse cardiovascular outcomes as well as incident hospitalization for heart failure.

Topics: Aged; Antihypertensive Agents; Cardiovascular System; Coronary Artery Disease; Female; Follow-Up Studies; Humans; Indoles; Male; Middle Aged; Osteopontin; Prognosis; Risk Factors; Stroke Volume

The dyad of hypertension and coronary artery disease is prevalent; however, data on systolic blood pressure (SBP) control and long-term all-cause mortality are lacking. Using extended follow-up data from the US cohort of the International Verapamil (SR)/Trandolapril Study (mean 11.6 years), subjects were categorized by age at enrollment (50 to <60 and ≥60 years). Cox proportional adjusted hazard ratios (HRs) were constructed for time to all-cause mortality according to achieved mean SBP. In those 50 to <60 years and using a referent SBP of <130 mm Hg, an achieved SBP of 130 to 140 mm Hg was associated with a similar risk of mortality (HR, 1.03; 95% confidence interval [CI], 0.87-1.23), whereas an achieved SBP of ≥140 mm Hg was associated with an increased risk of mortality (HR, 1.80; 95% CI, 1.53-2.11). Among subjects aged ≥60 years and using a referent SBP of <130 mm Hg, an achieved SBP 130 to 140 mm Hg was associated with a lower mortality risk (HR, 0.92; 95% CI, 0.85-0.98). There was an increased risk of mortality with an achieved SBP ≥150 mm Hg (HR, 1.34; 95% CI, 1.23-1.45), but not with an achieved SBP 140 to 150 mm Hg (HR, 1.02; 95% CI, 0.94-1.11). In hypertensive patients with coronary artery disease, achieving a SBP of 130 to 140 mm Hg seems to be associated with lower all-cause mortality after ≈11.6 years of follow-up.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00133692.

Topics: Aged; Blood Pressure Determination; Cause of Death; Comorbidity; Coronary Artery Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypertension; Indoles; Internationality; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk Assessment; Survival Rate; Systole; Treatment Outcome; United States; Verapamil

Elevated nighttime blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged ≥ 50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001). Atenolol also decreased hourly HR (P<0.0001). Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively). Compared with verapamil SR, atenolol also increased the prevalence of BP and HR nighttime dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26-8.97 P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17; P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019). Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events.

Topics: Aged; Antihypertensive Agents; Atenolol; Blood Pressure; Coronary Artery Disease; Drug Therapy, Combination; Female; Heart Rate; Humans; Hypertension; Indoles; Male; Middle Aged; Monitoring, Ambulatory; Photoperiod; Prospective Studies; Verapamil

The aims of this study were to assess the prognostic value of cardiac troponin I levels, measured with a new high-sensitivity assay, in low-risk patients with stable coronary artery disease (CAD) and to contrast its determinants and prognostic merit with that of high-sensitivity cardiac troponin T (hs-TnT).. New, highly sensitive cardiac troponin assays permit evaluation of the association between troponin levels and outcomes in patients with stable CAD.. High-sensitivity cardiac troponin I (hs-TnI) levels at baseline were assessed in 3,623 patients with stable CAD and preserved systolic function enrolled in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy) trial.. In total, 98.5% of patients had hs-TnI concentrations higher than the detection level (1.2 pg/ml). hs-TnI correlated moderately with hs-TnT (r = 0.44) and N-terminal pro-B-type natriuretic peptide (r = 0.39) but only weakly with age (r = 0.17) and estimated glomerular filtration rate (r = -0.11). During a median follow-up period of 5.2 years, 203 patients died of cardiovascular causes or were hospitalized for heart failure, and 209 patients had nonfatal myocardial infarctions. In analyses adjusting for conventional risk markers, N-terminal pro-B-type natriuretic peptide, and hs-TnT, hs-TnI levels in the fourth compared with the 3 lower quartiles were associated with the incidence of cardiovascular death or heart failure (hazard ratio: 1.84; 95% confidence interval: 1.30 to 2.61; p < 0.001). [corrected]. There was a [corrected] weaker association with nonfatal myocardial infarction (hazard ratio: 1.37; 95% confidence interval: 0.98 to 1.92; p = 0.066). [corrected]. In the same models, hs-TnT concentrations were associated with the incidence of cardiovascular death or heart failure but not of myocardial infarction.. In patients with stable CAD, hs-TnI concentrations are associated with cardiovascular risk independently of conventional risk markers and hs-TnT. (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy [PEACE]; NCT00000558).

Topics: Age Factors; Angiotensin-Converting Enzyme Inhibitors; Cause of Death; Coronary Artery Disease; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Indoles; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Statistics as Topic; Survival Rate; Troponin I; United States

We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a β-blocker strategy or a calcium channel blocker strategy. Genome-spanning single nucleotide polymorphism (SNP)×treatment interaction analyses of nonsynonymous SNPs were conducted in white and Hispanic race/ethnic groups. Top hits from whites were tested in Hispanics for consistency. A genetic risk score was constructed from the top 3 signals and tested in the Nordic Diltiazem study. SIGLEC12 rs16982743 and A1BG rs893184 had a significant interaction with treatment strategy for adverse cardiovascular outcomes (INVEST whites and Hispanics combined interaction P=0.0038 and 0.0036, respectively). A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39×10(-5)). In patients with a genetic risk score of 0 or 1, calcium channel blocker treatment was associated with lower risk (odds ratio [95% confidence interval]=0.60 [0.42-0.86]), and in those with a genetic risk score of 2 to 3, calcium channel blocker treatment was associated with higher risk (odds ratio [95% confidence interval]=1.31 [1.08-1.59]). These results suggest that cardiovascular outcomes may differ based on SIGLEC12, A1BG, F5 genotypes, and antihypertensive treatment strategy. These specific genetic associations and our risk score provide insight into a potential approach to personalized antihypertensive treatment selection.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Case-Control Studies; Coronary Artery Disease; DNA; Factor V; Female; Follow-Up Studies; Genotype; Glycoproteins; Humans; Hypertension; Immunoglobulins; Indoles; Lectins; Male; Membrane Proteins; Middle Aged; Pharmacogenetics; Polymorphism, Single Nucleotide; Prognosis; Selectins; Treatment Outcome; Verapamil

Angina and hypertension are common in patients with coronary artery disease (CAD); however, the effect on mortality is unclear. We conducted this prespecified analysis of the International Verapamil/Trandolapril Study (INVEST) to assess relationships between angina, blood pressure (BP), and mortality among elderly, hypertensive CAD patients.. Angina and elevated BP will be associated with higher mortality.. Extended follow-up was performed using the National Death Index for INVEST patients in the United States (n = 16 951). Based on angina history at enrollment and during follow-up visits, patients were divided into groups: persistent angina (n = 7184), new-onset angina (n = 899), resolved angina (n = 4070), and never angina (n = 4798). Blood pressure was evaluated at baseline, during drug titration, and during follow-up on-treatment. On-treatment systolic BP was classified as tightly controlled (<130 mm Hg), controlled (130-139 mm Hg), or uncontrolled (≥140 mm Hg). A Cox proportional hazards model was created adjusting for age, heart failure, diabetes, renal impairment, myocardial infarction, stroke, and smoking. The angina groups and BP control groups were compared using the never-angina group as the reference.. Only in the persistent-angina group was a significant association with mortality observed, with an apparent protective effect (hazard ratio: 0.82, 95% confidence interval: 0.75-0.89, P < 0.0001). Uncontrolled BP was associated with increased mortality risk (hazard ratio: 1.29, 95% confidence interval: 1.20-1.40, P < 0.0001), as were several other known cardiovascular risk factors.. In hypertensive CAD patients, persistent angina was associated with lower mortality. The observed effect was small compared with other cardiovascular risk factors, such as BP, which were associated with increased mortality.

Topics: Age Factors; Aged; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Chi-Square Distribution; Coronary Artery Disease; Female; Humans; Hypertension; Indoles; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; United States; Verapamil

Due to time-dependent confounding by blood pressure and differential loss to follow-up, it is difficult to estimate the effectiveness of aggressive versus conventional antihypertensive combination therapies in non-randomized comparisons.. We utilized data from 22,576 hypertensive coronary artery disease patients, prospectively enrolled in the INternational VErapamil-Trandolapril STudy (INVEST). Our post-hoc analyses did not consider the randomized treatment strategies, but instead defined exposure time-dependently as aggressive treatment (≥3 concomitantly used antihypertensive medications) versus conventional treatment (≤2 concomitantly used antihypertensive medications). Study outcome was defined as time to first serious cardiovascular event (non-fatal myocardial infarction, non-fatal stroke, or all-cause death). We compared hazard ratio (HR) estimates for aggressive vs. conventional treatment from a Marginal Structural Cox Model (MSCM) to estimates from a standard Cox model. Both models included exposure to antihypertensive treatment at each follow-up visit, demographics, and baseline cardiovascular risk factors, including blood pressure. The MSCM further adjusted for systolic blood pressure at each follow-up visit, through inverse probability of treatment weights.. 2,269 (10.1%) patients experienced a cardiovascular event over a total follow-up of 60,939 person-years. The HR for aggressive treatment estimated by the standard Cox model was 0.96 (95% confidence interval 0.87-1.07). The equivalent MSCM, which was able to account for changes in systolic blood pressure during follow-up, estimated a HR of 0.81 (95% CI 0.71-0.92).. Using a MSCM, aggressive treatment was associated with a lower risk for serious cardiovascular outcomes compared to conventional treatment. In contrast, a standard Cox model estimated similar risks for aggressive and conventional treatments.. Clinicaltrials.gov Identifier: NCT00133692.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Confounding Factors, Epidemiologic; Coronary Artery Disease; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Indoles; Male; Middle Aged; Models, Structural; Proportional Hazards Models; Risk Factors; Treatment Outcome; Verapamil

Limited information exists regarding the association between subjective well-being (SWB) and systolic blood pressure (SBP) among hypertensive patients with coronary artery disease (CAD).. We tested the hypothesis that there is an association between SBP and SWB.. We studied 22,576 hypertensive CAD patients > or = 50 years old in the INternational VErapamil SR-Trandolapril Study (INVEST), a randomized, blinded-endpoint trial of antihypertensive therapy in stable CAD patients. At each study visit, patients rated their SWB in the previous 4 weeks as "excellent," "good," "fair," or "poor" prior to SBP recordings. The outcome measure was SWB of "fair" or "poor." A longitudinal analysis using generalized estimating equations was performed to assess the association between SBP and odds of reporting fair/poor SWB, controlling for baseline SWB of fair/poor and angina reported during the study.. Patients with higher SBP had higher odds of reporting fair/poor SWB. Specifically, compared with patients with SBP of < or = 120, patients with SBP 140-150 > 150 - < or = 160 and > 160 had about 90% and 2.5 times greater odds of feeling fair/poor, respectively (adjusted odds ratio [OR]: 1.5990, 95% confidence interval [CI]: 1.81-2.00 and adjusted OR: 2.53, 95% CI: 2.41-2.66). Those who reported angina in the 4 wks prior to a protocol visit had 2.2 times greater odds of reporting fair/poor SWB (adjusted OR: 2.2, 95% CI: 2.13-2.27). Female gender, black race, history of smoking, diabetes, myocardial infarction, stroke, and cancer also increased the odds of reporting fair/poor SWB.. Among hypertensive CAD patients, higher on-treatment SBP is associated with greater odds of fair/poor SWB during follow-up.

Topics: Aged; Antihypertensive Agents; Atenolol; Blood Pressure; Coronary Artery Disease; Drug Therapy, Combination; Female; Humans; Hypertension; Indoles; Male; Mental Health; Middle Aged; Odds Ratio; Quality of Life; Risk Assessment; Risk Factors; Surveys and Questionnaires; Systole; Time Factors; Treatment Outcome; Verapamil

Heart failure (HF) is a disease commonly associated with coronary artery disease. Most risk models for HF development have focused on patients with acute myocardial infarction. The Prevention of Events with Angiotensin-Converting Enzyme Inhibition population enabled the development of a risk model to predict HF in patients with stable coronary artery disease and preserved ejection fraction.. In the 8290, Prevention of Events with Angiotensin-Converting Enzyme Inhibition patients without preexisting HF, new-onset HF hospitalizations, and fatal HF were assessed over a median follow-up of 4.8 years. Covariates were evaluated and maintained in the Cox regression multivariable model using backward selection if P<0.05. A risk score was developed and converted to an integer-based scoring system. Among the Prevention of Events with Angiotensin-Converting Enzyme Inhibition population (age, 64+/-8; female, 18%; prior myocardial infarction, 55%), there were 268 cases of fatal and nonfatal HF. Twelve characteristics were associated with increased risk of HF along with several baseline medications, including older age, history of hypertension, and diabetes. Randomization to trandolapril independently reduced the risk of HF. There was no interaction between trandolapril treatment and other risk factors for HF. The risk score (range, 0 to 21) demonstrated excellent discriminatory power (c-statistic 0.80). Risk of HF ranged from 1.75% in patients with a risk score of 0% to 33% in patients with risk score >or=16.. Among patients with stable coronary artery disease and preserved ejection fraction, traditional and newer factors were independently associated with increased risk of HF. Trandolopril decreased the risk of HF in these patients with preserved ejection fraction.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Female; Heart Failure; Humans; Indoles; Kaplan-Meier Estimate; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Although sudden cardiac death (SCD) has been extensively studied in patients with coronary artery disease (CAD) and low ejection fraction, prediction of SCD among individuals with preserved left ventricular systolic function is less well understood. We randomized 8,290 patients with stable CAD with preserved left ventricular systolic function to trandolapril or placebo in a secondary coronary prevention trial, and we used Cox proportional hazards models to identify independent baseline predictors of SCD during 4.8 year follow-up (median). Using a risk scoring algorithm based on simple clinical characteristics, we were able to distinguish individuals at higher risk for SCD. Independent determinants of SCD included age (p <0.001), current angina pectoris (p = 0.002), ejection fraction >40% to <50% (as opposed to >50%) (p <0.001), and diuretic (p <0.001) and digitalis use (p <0.001). Negative predictors included having prior coronary revascularization (p = 0.01) and being female (p = 0.02) or Caucasian (p = 0.006). Trandolapril neither increased nor decreased SCD. Thus, among patients with stable CAD with preserved left ventricular systolic function receiving current standard-of-care including coronary revascularization, clinical characteristics can identify individuals at higher risk for SCD.

Topics: Age Factors; Algorithms; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Coronary Artery Disease; Death, Sudden, Cardiac; Digitalis Glycosides; Diuretics; Female; Humans; Indoles; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Revascularization; Proportional Hazards Models; Racial Groups; Risk Assessment; Sex Factors; Stroke Volume; Systole; Ventricular Function, Left

The majority of hypertensive patients require combination therapy to achieve BP goals. Guidelines recommend dual therapy in newly diagnosed patients with BP > 160/100mm Hg. Calcium channel blocker (CCB)/ACE inhibitor and beta-blocker (beta-adrenoceptor antagonists)/diuretic combinations are among regimens considered effective for BP control. ACE inhibitors, beta-blockers, and CCBs are recommended for use in patients after myocardial infarction (MI). Statistical modeling from INVEST (INternational VErapamil-Trandolapril STudy), suggests an association between dual and triple therapy and decreased risk of primary outcome ([PO] first occurrence of death, nonfatal MI, or nonfatal stroke) in patients with hypertension and coronary artery disease (CAD).. This study explores the utility of dual antihypertensive therapy by reporting BP and cardiovascular outcomes for INVEST patients who predominantly received either a CCB/ACE inhibitor or a beta-blocker/ diuretic regimen.. 1170 patients were selected for analysis. After 24 months of treatment, BP control (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI criteria) was 82.1% and 82.6% in the verapamil sustained release (SR) + trandolapril (Ve + Tr) and atenolol + hydrochlorothiazide (At + HCTZ) groups, respectively (p = 0.86). In Ve + Tr compared to At + HCTZ patients, adjusted risk for PO (hazard ratio [HR] 0.63; 95% CI 0.37, 1.05; p = 0.07) and unadjusted risks for secondary outcomes including death (HR 0.70; 95% CI 0.40, 1.25), total MI (HR 0.82; 95% CI 0.35, 1.90), total stroke (HR 0.81; 95% CI 0.25, 2.65) and new diabetes (HR 0.88; 95% CI 0.55, 1.41) were not statistically different.. This analysis shows that combination treatment with either Ve+ Tr or At +- HCTZ is effective in achieving BP control and produces similar outcomes in hypertensive patients with CAD.

Topics: Adrenergic beta-Antagonists; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Blood Pressure; Calcium Channel Blockers; Coronary Artery Disease; Diuretics; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Indoles; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Treatment Outcome; Verapamil

Factors such as age and race/ethnicity might influence blood pressure (BP) response to drugs. Therapeutic response to the angiotensin-converting enzyme inhibitor trandolapril used as add-on therapy to stable calcium channel blocker therapy with verapamil sustained release 240 mg was addressed in a racially/ethnically diverse group of 1,832 hypertensive patients with coronary artery disease. Furthermore, the association with a polymorphism (1166A-->C) in the angiotensin II type 1 receptor gene (AGTR1) was tested. BP response was compared between groups using analysis of covariance after adjustment for covariates associated with BP response. Genotyping was performed using polymerase chain reaction and pyrosequencing. Trandolapril decreased mean unadjusted systolic and diastolic BPs by -9.1 +/- 17.3 (SD) and -4.1 +/- 10.1 mm Hg, respectively. The percentage of patients with BP under control (<140/90 mm Hg) increased from 6.7% to 41.3% (p <0.0001). Adjusted BP response was significantly associated with age and baseline systolic and diastolic BP (p <0.0001). Whereas the decrease in systolic BP was more pronounced in younger patients, the opposite was observed for diastolic BP decrease. Diastolic BP response was also significantly associated with race. Specifically, the adjusted diastolic BP decrease was significantly smaller in Hispanics and blacks than whites (p = 0.0032 and p = 0.0069, respectively). However, Hispanics achieved a decrease in systolic BP and an increase in BP control similar to the other ethnic groups. There was no genetic association between AGTR1 1166A-->C genotype and BP response. In conclusion, trandolapril add-on therapy was effective in increasing BP control, with age and baseline BP associated with both systolic and diastolic BP response. Race was associated with diastolic BP response, although the difference is likely not to be clinically significant and AGTR1 genotype was not associated with BP response.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Confounding Factors, Epidemiologic; Coronary Artery Disease; Drug Therapy, Combination; Female; Gene Frequency; Genotype; Humans; Hypertension; Indoles; Male; Middle Aged; Polymorphism, Genetic; Puerto Rico; Receptor, Angiotensin, Type 1; Treatment Outcome; United States; Verapamil

Prospective data regarding blood pressure (BP) control and cardiovascular (CV) outcomes in Hispanic women are lacking.. We analyzed 5017 Hispanic and 4710 non-Hispanic white hypertensive women with coronary artery disease (CAD) in the INternational VErapamil SR/Trandolapril STudy (INVEST) to determine the impact of baseline characteristics and BP control on CV outcomes.. At baseline, Hispanic women were younger and a had lower prevalence of most established CV risk factors than non-Hispanic white women. At 24 months, BP control (< 140/90 mm Hg) was achieved in 75% of Hispanic and 68% of non-Hispanic white women, (p < 0.001), with most women, regardless of ethnicity, requiring > or =2 antihypertensive agents. Following 26,113 patient-years of follow-up, the primary outcome (first occurrence of nonfatal myocardial infarction [MI], nonfatal stroke, or all cause death) occurred in 5.7% of Hispanic and 12.3% of non-Hispanic white women (adjusted HR = 0.84, 95% CI = 0.71-0.98, p = 0.03). There was no difference in outcome in either group of women comparing the randomized antihypertensive treatment strategies.. Despite accounting for a lower risk profile, deployment of protocol-based antihypertensive treatment regimens resulted in superior BP control and fewer CV events in Hispanic women compared with non-Hispanic white women.

Topics: Adult; Antihypertensive Agents; Blood Pressure; Confidence Intervals; Coronary Artery Disease; Female; Follow-Up Studies; Hispanic or Latino; Humans; Hydrochlorothiazide; Hypertension; Indoles; Middle Aged; Odds Ratio; Proportional Hazards Models; Treatment Outcome; White People; Women's Health

The purpose of this study was to assess the association between B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the incidence of specific cardiovascular events in low-risk patients with stable coronary disease, the incremental prognostic information obtained from these two biomarkers compared with traditional risk factors, and their ability to identify patients who may benefit from angiotensin-converting enzyme (ACE) inhibition.. The prognostic value of BNPs in low-risk patients with stable coronary artery disease remains unclear.. Baseline plasma BNP and NT-proBNP concentrations were measured in 3,761 patients with stable coronary artery disease and preserved left ventricular function participating in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibition) study, a placebo-controlled trial of trandolapril. Multivariable Cox regression was used to assess the association between natriuretic peptide concentrations and the incidence of cardiovascular mortality, fatal or nonfatal myocardial infarction, heart failure, and stroke.. The BNP and NT-proBNP levels were strongly related to the incidence of cardiovascular mortality, heart failure, and stroke but not to myocardial infarction. In multivariable models, BNP remained associated with increased risk of heart failure, whereas NT-proBNP remained associated with increased risk of cardiovascular mortality, heart failure, and stroke. By C-statistic calculations, BNP and NT-proBNP significantly improved the predictive accuracy of the best available model for incident heart failure, and NT-proBNP also improved the model for cardiovascular death. The magnitude of effect of ACE inhibition on the likelihood of experiencing cardiovascular end points was similar, regardless of either BNP or NT-proBNP baseline concentrations.. In low-risk patients with stable coronary artery disease and preserved ventricular function, BNPs provide strong and incremental prognostic information to traditional risk factors.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Humans; Indoles; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Probability; Prognosis; Proportional Hazards Models; Risk Assessment; Severity of Illness Index; Survival Analysis; Treatment Outcome

Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function.. We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13).. Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Chronic Disease; Coronary Artery Disease; Female; Glomerular Filtration Rate; Humans; Indoles; Male; Middle Aged; Renal Insufficiency; Survival Analysis; Treatment Outcome

Knowledge of predictors of diabetes mellitus (DM) development in patients with coronary artery disease (CAD) who use antihypertensive therapy could contribute to decreasing this adverse metabolic consequence. This is particularly relevant because the standard of care, beta blockers combined with diuretics, may contribute to adverse metabolic risk. The INternational VErapamil SR-trandolapril STudy compared a calcium antagonist-based (verapamil SR) and a beta-blocker-based (atenolol) strategy with trandolapril and/or hydrochlorothiazide added to control blood pressure (BP) in patients with CAD. The 16,176 patients without DM at entry were investigated with regard to newly diagnosed DM during follow-up. Newly diagnosed DM was less frequent in the verapamil SR versus atenolol strategy (7.0% vs 8.2%, hazard ratio 0.85, 95% confidence interval 0.76 to 0.95, p <0.01). Characteristics associated with risk for newly diagnosed DM included United States residence, left ventricular hypertrophy, previous stroke/transient ischemic attack, Hispanic ethnicity, coronary revascularization, hypercholesterolemia, greater body mass index, and higher follow-up systolic BP. Addition of trandolapril to verapamil SR decreased DM risk and addition of hydrochlorothiazide to atenolol increased risk. In conclusion, clinical findings associated with more severe vascular disease and Hispanic ethnicity identify a group at high risk for developing DM, whereas lower on-treatment BP and treatment with verapamil SR-trandolapril attenuated this risk.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Atenolol; Body Mass Index; Calcium Channel Blockers; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Female; Follow-Up Studies; Hispanic or Latino; Humans; Hydrochlorothiazide; Hypercholesterolemia; Hypertrophy, Left Ventricular; Indoles; Ischemic Attack, Transient; Male; Myocardial Revascularization; Residence Characteristics; Risk Factors; Stroke; Systole; Verapamil

Angiotensin-converting enzyme inhibitor therapy provides positive outcome benefits in a number of cardiac scenarios including congestive heart failure, postmyocardial infarction, as well as in the hypertensive patient at cardiac risk. This benefit exists both in normotensive and hypertensive individuals and is present in those with various grades of cardiovascular risk. This beneficial cardiovascular effect has now been observed with several angiotensin-converting enzyme inhibitors, suggesting a class effect. The Prevention of Events with Angiotensin-Converting Enzyme Inhibition trial studied the effect of adding the angiotensin-converting enzyme inhibitor trandolapril to a contemporary therapeutic regimen of patients with stable coronary artery disease and preserved left ventricular function. In this study, the addition of trandolapril did not confer any additional benefit in terms of reducing the incidence of cardiovascular death, myocardial infarction, or coronary revascularization. The neutral findings in this trial add a new wrinkle to the concept of class effect for cardiovascular protection with angiotensin-converting enzyme inhibitors in patients with coronary artery disease.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Indoles; Male; Middle Aged; Treatment Outcome

The INternational VErapamil SR-Trandolapril Study (INVEST), a prospective, randomized, antihypertensive trial, found that two different medication regimens produced similar blood pressure (BP) control with equivalent cardiovascular (CV) outcomes (death from any cause, nonfatal myocardial infarction [MI], or nonfatal stroke).. The study was undertaken to investigate whether differences exist by global regions in demographics, treatment, and outcomes in the INVEST trial.. Data were analyzed for 22,576 patients with stable coronary artery disease (CAD) enrolled in INVEST. We investigated differences in patient characteristics, treatment approaches, BP control, and clinical outcomes by creating three global regions based on geographical location: Northern Americas (NA), Caribbean (CA), and Eurasia (EA).. We observed significant regional differences in patient characteristics, treatment patterns, BP control, and CV outcomes. At baseline, patients from NA were older and had greater body mass index, higher rates of diabetes, peripheral vascular disease, and coronary revascularization, but lower rates of MI or left ventricular hypertrophy than patients in CA and EA. At 24 months, there were regional differences in both study and nonstudy antihypertensive drug use. Despite having higher mean baseline BP, patients from CA and EA achieved lower mean systolic BP throughout study follow-up. Furthermore, patients from both CA and EA had lower rates of all-cause mortality, fatal or nonfatal MI, fatal or nonfatal stroke, and newly diagnosed diabetes than patients from NA.. In INVEST, regional differences in medication utilization, BP control, and CV outcomes were identified. These disparities warrant further investigation to define appropriate care for patients with hypertension and stable CAD from an international public health perspective.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Body Mass Index; Calcium Channel Blockers; Coronary Artery Disease; Female; Follow-Up Studies; Humans; Hypertension; Indoles; Male; Middle Aged; Prospective Studies; Treatment Outcome; Verapamil

Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials.. To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non-calcium antagonist strategy (NCAS).. Randomized, open label, blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries.. Patients were randomly assigned to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment.. Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months.. At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies (9.93% in CAS and 10.17% in NCAS; relative risk [RR], 0.98; 95% confidence interval [CI], 0.90-1.06). Two-year blood pressure control was similar between groups. The JNC VI blood pressure goals were achieved by 65.0% (systolic) and 88.5% (diastolic) of CAS and 64.0% (systolic) and 88.1% (diastolic) of NCAS patients. A total of 71.7% of CAS and 70.7% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg.. The verapamil-trandolapril-based strategy was as clinically effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Blood Pressure; Calcium Channel Blockers; Coronary Artery Disease; Diuretics; Drug Therapy, Combination; Female; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Indoles; Male; Middle Aged; Sodium Chloride Symporter Inhibitors; Treatment Outcome; Verapamil

Accumulating evidence indicates that higher blood pressure (BP) variability from one physician office visit to the next (hereafter referred to as visit-to-visit BP variability) is associated with poor outcomes. Short-term measurement (throughout 1 year) of visit-to-visit BP variability in high-risk older patients may help identify patients at increased risk of death.. To evaluate whether short-term visit-to-visit BP variability is associated with increased long-term mortality risk.. The US cohort of the International Verapamil SR-Trandolapril Study (INVEST), a randomized clinical trial of 16 688 patients aged 50 years or older with hypertension and coronary artery disease, was conducted between September 2, 1997, and December 15, 2000, with in-trial follow-up through February 14, 2003. The study evaluated a calcium antagonist (sustained-release verapamil plus trandolapril) vs β-blocker (atenolol plus hydrochlorothiazide) treatment strategy. Blood pressure measurement visits were scheduled every 6 weeks for the first 6 months and biannually thereafter. Statistical analysis was performed from September 2, 1997, to May 1, 2014.. Visit-to-visit systolic BP (SBP) and diastolic BP variability during the first year of enrollment using 4 different BP variability measures: standard deviation, coefficient of variation, average real variability, and variability independent of the mean.. All-cause death, assessed via the US National Death Index, beginning after the exposure assessment period through May 1, 2014.. For the present post hoc analysis, long-term mortality data were available on 16 688 patients (9001 women [54%]; mean [SD] age, 66.5 [9.9] years; 45% White patients, 16% Black patients, and 37% Hispanic patients). During a mean (SD) follow-up of 10.9 (4.2) years, 5058 patients (30%) died. All 4 variability measures for SBP were significantly associated with long-term mortality after adjustment for baseline demographic characteristics and comorbidities. After comparison of lowest vs highest variability measure quintiles, the magnitude of the association with death remained statistically significant even after adjustment for baseline demographic characteristics and comorbidities (average real variability: adjusted hazard ratio [aHR], 1.18; 95% CI, 1.08-1.30; standard deviation: aHR, 1.14; 95% CI, 1.04-1.24; coefficient of variation: aHR, 1.15; 95% CI, 1.06-1.26; variability independent of the mean: aHR, 1.15; 95% CI, 1.05-1.25). The signal was stronger in women compared with men. Associations of diastolic BP variability measures with death were weaker than for SBP and were not significant after adjustment.. This study suggests that, in a large population of older patients with hypertension and coronary artery disease, short-term visit-to-visit SBP variability was associated with excess long-term mortality, especially for women. Efforts to identify and minimize visit-to-visit SBP variability may be important in reducing excess mortality later in life.. ClinicalTrials.gov Identifier: NCT00133692.

Topics: Aged; Antihypertensive Agents; Atenolol; Blood Pressure; Coronary Artery Disease; Female; Humans; Hydrochlorothiazide; Hypertension; Indoles; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Proportional Hazards Models; Randomized Controlled Trials as Topic; Sex Factors; Verapamil

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cohort Studies; Coronary Artery Disease; Female; Humans; Hypertension; Indoles; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; Treatment Outcome; Verapamil

Topics: Blood Pressure; Coronary Artery Disease; Female; Humans; Hypertension; Indoles; Verapamil

A goal SBP 120 mmHg or less reduced mortality in high-risk Systolic Blood Pressure Intervention Trial patients; however, mortality implications of concomitant DBP lowering in coronary artery disease (CAD) are uncertain. We examined the relationship between DBP lowering and all-cause mortality with lower achieved SBPs in a large cohort.. We categorized 17 131 hypertensive patients from the INternational VErapamil-trandolapril STudy US cohort, aged at least 50 years with CAD, by mean achieved SBP (<120, 120 to <130, 130 to <140, and ≥140 mmHg) and DBP tertiles (low, middle, and high per SBP category) during active follow-up. Long-term mortality was determined via National Death Index. Multivariable Cox regression was performed to investigate the impact of DBP lowering among all SBP categories and within each SBP category.. There were 6031 deaths over mean follow-up of 11.6 years (198 352 patient-years). In unadjusted analyses, achieving DBP in the lowest tertile portended greatest mortality risk across all SBP categories. In multivariate analysis, using SBP 120 to less than 130 mmHg, DBP at least 79 mmHg as reference (mortality nadir), achieving DBP in the lowest tertile (DBP < 69 mmHg) was associated with excess mortality risk among those with SBP less than 120 mmHg (adjusted hazard ratio 1.60; 95% confidence interval, 1.33-1.91). However, among those with SBP 120 to less than 140 mmHg, adjusted mortality risk did not differ significantly with low DBPs. Among those with SBP at least 140 mmHg, mortality risk remained high regardless of DBP.. In older CAD patients, the mortality risk related to excess DBP lowering is accentuated in those achieving intensive SBP control less than 120 mmHg, raising concerns about intensive SBP lowering in these patients.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Coronary Artery Disease; Diastole; Female; Follow-Up Studies; Humans; Hypertension; Indoles; Male; Middle Aged; Multicenter Studies as Topic; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Systole; Time Factors; United States; Verapamil

Women are at greater risk of developing resistant hypertension (RH) than men, yet scarce data exist on RH-associated outcomes in women. We aimed to determine all-cause mortality risk associated with apparent RH (aRH) among women across the spectrum of underlying coronary disease.. We analyzed data from St. James Women Take Heart (WTH; women without coronary disease at baseline), Women's Ischemia Syndrome Evaluation (women with signs/symptoms of ischemia at baseline), and the INternational VErapamil-Trandolapril STudy (INVEST; women with coronary artery disease and hypertension at baseline), totaling 15,108 adult women with no hypertension, non-RH (blood pressure [BP] ≥140/90 mmHg on ≤2 drugs or BP <140/90 mmHg on 1-3 drugs), or aRH (BP ≥140/90 mmHg on ≥3 drugs or anyone on ≥4 drugs) at baseline. The primary outcome was all-cause mortality.. Prevalence of aRH ranged from 0.4% (WTH) to 10.6% (INVEST). Women with aRH, compared to those without, were older, more often black, and more likely to be obese or diabetic. Pooling all cohorts, risk for all-cause death was greater in women with aRH than in women with non-RH (adjusted HR 1.40; 95% CI 1.27-1.55) and women without hypertension (adjusted HR 2.34; 95% CI 1.76-3.11) over a median follow-up of 14.3 years.. aRH prevalence in women varies according to underlying coronary disease, and aRH is associated with a substantial, early, and sustained increased risk of all-cause death. Additional research into early recognition and prevention strategies for RH are needed, especially in black and older women, and those with known cardiovascular risk factors.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Coronary Artery Disease; Drug Resistance; Female; Humans; Hypertension; Indoles; Middle Aged; Myocardial Ischemia; Obesity; Prospective Studies; Risk Factors; Stroke; Treatment Outcome; United States; Verapamil

We used data from patients with stable coronary artery disease (CAD) to assess the risk of new-onset diabetes mellitus (NOD) with β blockers and to determine whether angiotensin-converting enzyme (ACE) inhibition would modify this risk. The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) trial randomized 8,290 patients with stable CAD to trandolapril or placebo. Presence of NOD was assessed at each study visit over a median follow-up time of 4.8 years. We examined the risk of NOD associated with β-blocker use with Cox regression models adjusting for 25 baseline covariates and tested whether this risk was modified by randomization to the ACE inhibitor. Of 6,910 patients without diabetes mellitus at enrollment (1,179 women and 5,731 men, mean age 64 ± 8 years), 4,147 (60%) were taking β blockers and 733 (8.8%) developed NOD. We observed a significant interaction between β-blocker use and randomization to ACE inhibitor with respect to NOD (p = 0.028). Participants taking β blockers assigned to the placebo group (n = 2,090) were at increased risk for NOD adjusting for baseline covariates (hazard ratio 1.63, 95% confidence interval 1.29 to 2.05, p <0.001), and this risk was attenuated in those assigned to trandolapril (n = 2,057, hazard ratio 1.11, 95% confidence interval 0.87 to 1.42, p = 0.39). β blocker use was associated with increased risk for NOD in patients with stable CAD, and this risk was decreased in patients treated concurrently with an ACE inhibitor. In conclusion, these data suggest that ACE inhibition may attenuate the risk for glucose abnormalities observed in patients taking β blockers.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Coronary Artery Disease; Diabetes Mellitus; Female; Humans; Indoles; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors

There is limited information about the safety of chronic nonsteroidal anti-inflammatory drugs (NSAIDs) in hypertensive patients with coronary artery disease.. This was a post hoc analysis from the INternational VErapamil Trandolapril STudy (INVEST), which enrolled patients with hypertension and coronary artery disease. At each visit, patients were asked by the local site investigator if they were currently taking NSAIDs. Patients who reported NSAID use at every visit were defined as chronic NSAID users, while all others (occasional or never users) were defined as nonchronic NSAID users. The primary composite outcome was all-cause death, nonfatal myocardial infarction, or nonfatal stroke. Cox regression was used to construct a multivariate analysis for the primary outcome.. There were 882 chronic NSAID users and 21,694 nonchronic NSAID users (n = 14,408 for never users and n=7286 for intermittent users). At a mean follow-up of 2.7 years, the primary outcome occurred at a rate of 4.4 events per 100 patient-years in the chronic NSAID group, versus 3.7 events per 100 patient-years in the nonchronic NSAID group (adjusted hazard ratio [HR] 1.47; 95% confidence interval [CI], 1.19-1.82; P=.0003). This was due to an increase in cardiovascular mortality (adjusted HR 2.26; 95% CI, 1.70-3.01; P<.0001).. Among hypertensive patients with coronary artery disease, chronic self-reported use of NSAIDs was associated with an increased risk of adverse events during long-term follow-up.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Blood Pressure; Celecoxib; Confounding Factors, Epidemiologic; Coronary Artery Disease; Diclofenac; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypertension; Ibuprofen; Indoles; Kaplan-Meier Estimate; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Myocardial Infarction; Naproxen; Odds Ratio; Proportional Hazards Models; Pyrazoles; Randomized Controlled Trials as Topic; Stroke; Sulfonamides; Verapamil

Our understanding of the growing population of revascularized patients with hypertension is limited. We retrospectively analyzed the International Verapamil SR-Trandolapril Study, which randomized coronary artery disease patients with hypertension to either verapamil SR- or atenolol-based treatment strategies, focusing on characteristics and outcomes of 6166 previously revascularized patients compared with 16 410 nonrevascularized patients. Revascularized patients had a history of coronary artery bypass grafting (45.2%), percutaneous coronary intervention (42.1%), or both (12.8%). Compared with nonrevascularized patients, revascularized patients at baseline demonstrated a higher prevalence of coronary artery disease risk factors and risk conditions (P<0.001). This higher prevalence was the principal cause of a higher incidence of primary outcome (death, nonfatal myocardial infarction, or nonfatal stroke) among revascularized patients (14.2% versus 8.5% for nonrevascularized patients; P<0.001). However, both patient groups demonstrated a relatively low incidence of subsequent revascularization (5.1% versus 1.5% respectively; P<0.0001). Associations between adjusted hazard ratio for primary outcome and follow-up blood pressure appeared "J shaped" for both patient groups. Because, as a group, revascularized patients with hypertension had worse outcomes compared with nonrevascularized patients, management of blood pressure to a specific target in future studies could result in improved outcomes.

Topics: Aged; Angioplasty, Balloon, Coronary; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Hypertension; Incidence; Indoles; Male; Middle Aged; Prevalence; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome; Verapamil

The International Verapamil SR-Trandolapril Study (INVEST), a randomized trial of 22,576 predominantly elderly patients with an average 2.7-year follow-up, compared a calcium antagonist-led strategy (verapamil SR plus trandolapril) with a beta-blocker-led strategy (atenolol plus hydrochlorothiazide) for hypertension treatment and prevention of cardiovascular outcomes in coronary artery disease patients. Patients received individualized dose and drug titration following a flexible, multi-drug, guideline-based treatment algorithm, with the objective of achieving optimal blood pressure (BP) control individualized for comorbidities (e.g., diabetes). The primary outcome (PO) was first occurrence of death (all-cause), nonfatal myocardial infarction or nonfatal stroke. The strategies resulted in significant and very similar BP reduction, with approximately 70% of patients in both strategies achieving BP control (<140/90 mmHg). Increasing number of office visits with BP in control was associated with reduced risk of the PO. Overall, there was no difference in the PO comparing the strategies; however, new-onset diabetes occurred more frequently in those assigned the atenolol strategy. This report summarizes findings from INVEST and puts them in perspective with our current state of knowledge derived from other large hypertension treatment trials. INVEST findings support that BP reduction is important for prevention of adverse cardiovascular morbidity and mortality, and selection of antihypertensive agents should be based on patient comorbidities and other risk factors (e.g., risk for diabetes) and not necessarily that any one drug be given to all.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Atenolol; Calcium Channel Blockers; Coronary Artery Disease; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diuretics; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Indoles; Male; Randomized Controlled Trials as Topic; Verapamil

Our understanding of factors influencing stroke risk among patients with coronary artery disease is incomplete. Accordingly, factors predicting stroke risk in hypertensive, clinically stable coronary artery disease patients were determined with data from the INternational VErapamil SR-trandolapril STudy (INVEST).. The effect of baseline characteristics and on-treatment blood pressure (BP) were analyzed to determine the risk of stroke (fatal or nonfatal) among the 22 576 patients enrolled. Cox proportional-hazards models (unadjusted, adjusted, and time dependent) were used to identify predictors of stroke among subgroups with these characteristics present at entry and on-treatment BP.. Excellent BP control (at 24 months, >70% <140/90 mm Hg) was achieved during 61 835 patient-years of follow-up, as 377 patients had a stroke (6.1 strokes/1000 patient-years) and 28% of those patients had a fatal stroke. Increased age, black race, US residency, and history of prior myocardial infarction, smoking, stroke/transient ischemic attack, arrhythmia, diabetes, and coronary bypass surgery were associated with an increased risk of stroke. Achieving a systolic BP <140 mm Hg and a diastolic BP <90 mm Hg was associated with a decreased risk of stroke. There was no statistically significant difference in stroke risk comparing the verapamil SR-based with the atenolol-based treatment strategy (adjusted hazard ratio=0.87; 95% CI, 0.71 to 1.06; P=0.17).. Among hypertensive patients with chronic coronary artery disease, stroke was an important complication associated with significant mortality. Black race, US residency, and conditions associated with increased vascular disease severity and arrhythmia predicted increased stroke risk, whereas achieving a BP <140/90 mm Hg on treatment predicted a reduced stroke risk.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Atenolol; Black People; Coronary Artery Disease; Databases, Factual; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Indoles; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Stroke; United States; Verapamil

We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease (CAD).. Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood. The INternational VErapamil-trandolapril STudy (INVEST) compared outcomes in hypertensive patients with CAD that were assigned randomly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added agents. During follow-up (61,835 patient-years), BP control and the primary outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not different between strategies.. We investigated risk for adverse outcome associated with baseline factors, follow-up BP, and drug treatments using Cox modeling.. Previous heart failure (adjusted hazard ratio [HR] 1.96), as well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61), renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR 1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively) and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with reduced risk.. In hypertensive patients with CAD, increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function. Lower follow-up BP and addition of trandolapril to verapamil SR each were associated with reduced risk.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Blood Pressure; Calcium Channel Blockers; Coronary Artery Disease; Humans; Hypertension; Indoles; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Risk Factors; Stroke; Verapamil

The results of the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE trial), involving patients with stable coronary heart disease, demonstrated that the angiotensin-converting enzyme (ACE) inhibitor trandolapril did not reduce cardiovascular mortality, or the incidence of fatal or non-fatal myocardial infarction. These results were in conflict with the vast majority of previously published large-scale trials, and could be seen to weaken confidence in ACE inhibitor therapy of ischaemic heart disease. This review article examines the results of PEACE in comparison with the other major trials in terms of the severity of the disease in the patients, the statistical power of the analyses, the doses of the agents used and the concept of a 'class effect' of the ACE inhibitors.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Coronary Artery Disease; Female; Humans; Indoles; Male; Middle Aged; Poland; Treatment Outcome

Topics: Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Coronary Artery Disease; Diastole; Humans; Hydrochlorothiazide; Indoles; Randomized Controlled Trials as Topic; Systole; Verapamil

The INternational VErapamil SR-Trandolapril study (INVEST) had 6400 of 22,576 (28.3%) participants with diabetes at entry. The objectives of this prespecified analysis were to compare antihypertensive treatment strategies in the diabetes cohort (verapamil SR-based [n=3169] versus atenolol-based [n=3231]) and identify predictors for the primary outcome (a composite of first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke). During a mean follow-up of 2.7 years, 913 participants with diabetes experienced a primary outcome event, with no significant difference between treatment strategies (14.6%, verapamil SR versus 13.9%; atenolol hazard ratio, 1.05; 95% confidence interval, 0.92 to 1.19). Risk for the primary outcome increased with presence of baseline heart failure, renal impairment, US residency, age, previous stroke/transient ischemic attack, previous myocardial infarction, peripheral vascular disease, or smoking. High systolic and diastolic pressures during follow-up also were associated with increased risk, as were low diastolic pressures. Antihypertensive treatment with a verapamil SR or atenolol strategy resulted in similar rates of cardiovascular outcomes in coronary artery disease (CAD) patients with diabetes. Thus, a verapamil SR-based antihypertensive treatment strategy is an alternative to a beta-blocker-based strategy in adults with CAD and diabetes.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atenolol; Calcium Channel Blockers; Coronary Artery Disease; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hypertension; Indoles; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome; Verapamil